Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review

SIMPLE SUMMARY: Neuroendocrine tumors (NETs) have become increasingly common. There are several effective treatment options for advanced NETs. However, there are limited clinical trial data and published practical information on how these different treatments should be sequenced. This review assesses randomized, controlled clinical trial data in advanced NETs to provide an expert perspective on treatment sequencing for important clinical scenarios, ranging from local disease to high-volume metastatic NETs. The best practices provided in this review may be useful for clinicians considering treatment options and sequencing for their patients with advanced NETs. ABSTRACT: Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data.